Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR- pigs challenged with an F4+ ETEC/VTEC/EPEC strain.

Dong Zhou,Wen-Yi Fan,Bent Borg Jensen,Meng-Ling Wang,Wei Zhang,Jiu-Feng Wang,Dan Song,Gui-Yan Yang,Yao-Hong Zhu

doi:10.1186/s13567-015-0223-y

Dong Zhou, Wen-Yi Fan + Show 7 more

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https://doi.org/10.1186/s13567-015-0223-y

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Abstract

Although breeding of F4 receptor − negative (F4R−) pigs may prevent post-weaning diarrhea, the underlying immunity is poorly understood. Here, various doses of a Bacillus licheniformis and Bacillus subtilis mixture (BLS-mix) were orally administered to F4ab/acR− pigs for 1 week before F4 (K88) − positive ETEC/VTEC/EPEC challenge. Administration of BLS-mix increased the percentage of Foxp3−IL-10+ T cells but not of Foxp3+IL-10+ regulatory T (Treg) cells among peripheral blood CD4+ T cells. A low dose of BLS-mix feeding resulted in increased the expression of IL-6, TNF-α, IL-10, and the transcription factors Foxp3 and T-bet mRNAs in the jejunum. Administration of either a low or high dose BLS-mix also led to an increase in the percentage of CD4+Foxp3+ Treg cells among intraepithelial lymphocytes and CD4+IL-10+ T cells in the small intestinal Peyer’s patches and the lamina propria of F4ab/acR− pigs following F4+ ETEC/VTEC/EPEC challenge. The increased number of IL-10–producing CD4+ T cells was attributed to an increase in the proportion of Foxp3−IL-10+ Treg cells rather than Foxp3+IL-10+ Treg cells. Our data indicate that oral administration of BLS-mix to newly weaned F4ab/acR− pigs ameliorates enteritis in an F4+ ETEC/VTEC/EPEC model; however, induction of IL-10–producing Foxp3− Treg cells by BLS-mix administration cannot account for the protection of newly weaned F4ab/acR− pigs from F4+ ETEC/VTEC/EPEC infection, and that excessive generation of CD4+IL-10+ T cells following consumption of BLS-mix during episodes of intestinal inflammation that is caused by enteric pathogens might prohibit clearance of the pathogen. Select probiotic mixtures may allow for tailoring strategies to prevent infectious diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0223-y) contains supplementary material, which is available to authorized users.

Highlights

Enterotoxigenic Escherichia coli (ETEC) harboring F4 (K88)+ fimbriae are a common cause of diarrhea in neonatal and newly weaned pigs [1]
We examined the effects of a select probiotic mixture comprised of Bacillus licheniformis and Bacillus subtilis (BLS-mix) on the populations of CD4+Foxp3+ regulatory T cell (Treg) and T regulatory type 1 cell (Tr1) cells in the small intestine of newly weaned F4ab/acR− pigs following F4+ ETEC/ verocytotoxigenic Escherichia coli (VTEC)/enteropathogenic Escherichia coli (EPEC) challenge
We detected a transient increase in the serum TNF-α concentration in F4 ab/acR− pigs after inoculation with F4+ ETEC/VTEC/EPEC, but this increase did not extend beyond 12 h post-challenge

Summary

Introduction

Enterotoxigenic Escherichia coli (ETEC) harboring F4 (K88)+ fimbriae are a common cause of diarrhea in neonatal and newly weaned pigs [1]. Adhesion of ETEC to the intestinal epithelium is a very complex process that may involve several structures including fimbriae and flagella [2]. Attachment of F4 fimbriae to specific F4 receptors on the porcine intestinal brush border is the first step in the infection process. The exact mutation causing susceptibility to F4+ ETEC remains unknown, a polymorphism within an intron of the mucin 4 (MUC4) gene on porcine chromosome 13 has been proposed as a candidate gene for the production of the specific ETEC F4ab/ac receptor, and a DNA marker − based test has been developed to allow genotyping for determining ETEC F4ab/ac resistance/

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